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| Status |
Public on Dec 15, 2020 |
| Title |
Regulation of anti-tumorigenic pathways by the combinatory treatment of calcitriol and TGF-β in PC-3 cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Calcitriol and transforming growth factors beta (TGF-β) are involved in several biological pathways such as cell proliferation, differentiation, migration and invasion. Their cellular effects could be similar or opposite depending on the genetic target, cell type and context. Despite the reported association of calcitriol deficiency and disruption of the TGF-β pathway in prostate cancer and the well-known independent effects of calcitriol and TGF-βs on cancer cells, there is limited information regarding the cellular effects of calcitriol and TGF-β in combination. In this study, we in vitro analyze the combinatory effects of calcitriol and TGF-β on cell growth and apoptosis using PC-3 and DU145 human prostate cancer cell lines. Using high-throughput microarray profiling of PC-3 cells upon independent and combinatory treatments, we identified distinct transcriptional landscapes of each intervention, with a higher effect established by the combinatorial treatment, following by TGF-β1 and later by calcitriol. A set of genes and enriched pathways converge among the treatments, mainly between the combinatory scheme and TGF-β1, but the majority were treatment-specific. Of note, CYP24A1, IGFBP3, SERPINE1, CDKN1A, NOX4 and UBE2D3 were significantly up-regulated upon the combinatorial treatment whereas CCNA1, members of the CT45A and APOBEC3 family were down-regulated. By public RNA signatures, we were able to confirm the regulation by the co-treatment over cell proliferation and cell cycle. We finally investigated the possible clinical impact of genes modulated by the combinatorial treatment using benchmark prostate cancer data. This comprehensive analysis reveals that the combinatory treatment impairs cell growth without affecting apoptosis and their combinatory actions might synergize and improved their individual effects to reprogram prostate cancer signaling.
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| Overall design |
PC-3 human prostate cancer cells were treated during 24hrs with calcitriol (10 nM) with TGF-β1 (5 ng/mL), alone or in combination. Gene expression profiles were evaluates on Clariom D (Affymetrix) microarrays.
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| Contributor(s) |
García-Olivares M, Romero-Córdoba S, Ortíz-Sánchez E, García-Becerra R, Segovia-Mendoza M, Rangel-Escareño C, Halhali A, Larrea F, Barrera D |
| Citation(s) |
33582304 |
| Submission date |
Oct 06, 2020 |
| Last update date |
Mar 16, 2021 |
| Contact name |
Sandra Lorena Romero-Cordoba |
| E-mail(s) |
sromero_cordoba@hotmail.com
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| Organization name |
National Instute of Genomic Medicine
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| Department |
Cancer Genomics
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| Street address |
Periférico Sur No. 4809, Col. Arenal Tepepan, Delegación Tlalpan. México, D.F.
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| City |
Mexico |
| State/province |
Mexico |
| ZIP/Postal code |
14610 |
| Country |
Mexico |
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| Platforms (1) |
| GPL23126 |
[Clariom_D_Human] Affymetrix Human Clariom D Assay [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA667722 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE159116_RAW.tar |
190.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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